Trial Outcomes & Findings for Xanthohumol Metabolism and Signature (NCT NCT03735420)

Last Updated: 2024-08-27

Results Overview

Circulating pro-inflammatory cytokine concentrations (tumor necrosis factor (TNF)-α, interleukin (IL)-1 beta, IL-6, IL-8, IL-10, and IL-12p70), will be measured simultaneously with a flow cytometry-based multiplex assay. The measures were assessed at Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks; weeks 2, 4, 6, and 8 reported

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Results posted on

2024-08-27

Participant Flow

Participant milestones

Participant milestones
Measure	Xanthohumol Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.	Placebo Oral Capsule Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.
Overall Study STARTED	16	14
Overall Study COMPLETED	16	14
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Xanthohumol Metabolism and Signature

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Xanthohumol n=16 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.	Placebo Oral Capsule n=14 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Total n=30 Participants Total of all reporting groups
Age, Continuous	29.06 years STANDARD_DEVIATION 6.45 • n=99 Participants	33.14 years STANDARD_DEVIATION 5.36 • n=107 Participants	30.97 years STANDARD_DEVIATION 6.22 • n=206 Participants
Sex: Female, Male Female	8 Participants n=99 Participants	8 Participants n=107 Participants	16 Participants n=206 Participants
Sex: Female, Male Male	8 Participants n=99 Participants	6 Participants n=107 Participants	14 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=99 Participants	13 Participants n=107 Participants	27 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	16 Participants n=99 Participants	12 Participants n=107 Participants	28 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	16 participants n=99 Participants	14 participants n=107 Participants	30 participants n=206 Participants
Body mass index	23.41 kilogram per meters-squared (kg/m2) STANDARD_DEVIATION 2.23 • n=99 Participants	23.30 kilogram per meters-squared (kg/m2) STANDARD_DEVIATION 2.57 • n=107 Participants	23.36 kilogram per meters-squared (kg/m2) STANDARD_DEVIATION 2.36 • n=206 Participants
Heart rate	64.50 beats per minute (bpm) STANDARD_DEVIATION 11.78 • n=99 Participants	61.07 beats per minute (bpm) STANDARD_DEVIATION 8.30 • n=107 Participants	62.90 beats per minute (bpm) STANDARD_DEVIATION 10.28 • n=206 Participants
Weight	69.82 kilograms STANDARD_DEVIATION 10.33 • n=99 Participants	70.60 kilograms STANDARD_DEVIATION 14.59 • n=107 Participants	70.18 kilograms STANDARD_DEVIATION 12.28 • n=206 Participants
Height	1.73 meters STANDARD_DEVIATION 0.12 • n=99 Participants	1.73 meters STANDARD_DEVIATION 0.11 • n=107 Participants	1.73 meters STANDARD_DEVIATION 0.12 • n=206 Participants

PRIMARY outcome

Timeframe: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Outcome measures

PRIMARY outcome

Timeframe: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Self-reported adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events. Reported as: New onset "FDA serious" adverse events (Grade 1); New onset "moderate" adverse events (Grade 2). The measures were assessed at Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks; weeks 2, 4, 6, and 8 reported.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=16 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=14 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Incidence of Intervention-attributable Adverse Events [Safety and Tolerability] Week 2 Grade 1	12 Adverse events	9 Adverse events
Incidence of Intervention-attributable Adverse Events [Safety and Tolerability] Week 2 Grade 2	2 Adverse events	2 Adverse events
Incidence of Intervention-attributable Adverse Events [Safety and Tolerability] Week 4 Grade 1	18 Adverse events	9 Adverse events
Incidence of Intervention-attributable Adverse Events [Safety and Tolerability] Week 4 Grade 2	0 Adverse events	3 Adverse events
Incidence of Intervention-attributable Adverse Events [Safety and Tolerability] Week 6 Grade 1	18 Adverse events	11 Adverse events
Incidence of Intervention-attributable Adverse Events [Safety and Tolerability] Week 6 Grade 2	8 Adverse events	2 Adverse events
Incidence of Intervention-attributable Adverse Events [Safety and Tolerability] Week 8 Grade 1	5 Adverse events	0 Adverse events
Incidence of Intervention-attributable Adverse Events [Safety and Tolerability] Week 8 Grade 2	2 Adverse events	2 Adverse events

SECONDARY outcome

Timeframe: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Xanthohumol and xanthohumol metabolites in blood, urine and stool, will be measured by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Metabolites include 6-prenylnaringenin (6-PN), 8-prenylnaringenin (8-PN), dihydroxanthohumol (DXN), desmethyldihydroxanthohumol (DDXN), isoxanthohumol (IXN), and xanthohumol (XN). The measures were assessed at Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks; baseline, weeks 2, 4, 6, and 8 reported for urine and plasma.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Bile acid concentrations in blood and feces, will be measured by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and expressed as mean change over time from baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Fecal calprotectin, a protein associated with gut inflammation and irritable gut syndrome, will be measured by enzyme-linked immunosorbent assay, and expressed as mean change over time from baseline.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=16 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=14 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Gut Inflammation Baseline	12.8 microgram per milligram (ug/mg) Standard Deviation 2.7	35.2 microgram per milligram (ug/mg) Standard Deviation 76.7
Gut Inflammation Week 2	12.4 microgram per milligram (ug/mg) Standard Deviation 1.5	19.9 microgram per milligram (ug/mg) Standard Deviation 21.8
Gut Inflammation Week 4	13.4 microgram per milligram (ug/mg) Standard Deviation 3.9	12.7 microgram per milligram (ug/mg) Standard Deviation 2.5
Gut Inflammation Week 6	12.7 microgram per milligram (ug/mg) Standard Deviation 2.5	14.3 microgram per milligram (ug/mg) Standard Deviation 5.4
Gut Inflammation Week 8	15.2 microgram per milligram (ug/mg) Standard Deviation 10.3	13.2 microgram per milligram (ug/mg) Standard Deviation 2.6

SECONDARY outcome

Timeframe: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Aspartate aminotransferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as mean change from baseline.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=16 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=14 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Aspartate Aminotransferase (AST) Week 2	22.9 milligrams per deciliter (mgdL) Standard Deviation 13.5	15.4 milligrams per deciliter (mgdL) Standard Deviation 2.6
Aspartate Aminotransferase (AST) Week 4	18.3 milligrams per deciliter (mgdL) Standard Deviation 5.1	15.3 milligrams per deciliter (mgdL) Standard Deviation 3.01
Aspartate Aminotransferase (AST) Week 6	21.1 milligrams per deciliter (mgdL) Standard Deviation 8.9	16.4 milligrams per deciliter (mgdL) Standard Deviation 3.2
Aspartate Aminotransferase (AST) Week 8	18.4 milligrams per deciliter (mgdL) Standard Deviation 5.8	15.5 milligrams per deciliter (mgdL) Standard Deviation 2.6

SECONDARY outcome

Timeframe: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Alanine aminotransferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as mean change from baseline.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=16 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=14 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Alanine Aminotransferase (ALT) Week 2	18.0 milligrams per decileter (mg/dL) Standard Deviation 15.1	14.9 milligrams per decileter (mg/dL) Standard Deviation 3.8
Alanine Aminotransferase (ALT) Week 4	16.1 milligrams per decileter (mg/dL) Standard Deviation 7.5	14.0 milligrams per decileter (mg/dL) Standard Deviation 3.81
Alanine Aminotransferase (ALT) Week 6	16.4 milligrams per decileter (mg/dL) Standard Deviation 7.5	15.4 milligrams per decileter (mg/dL) Standard Deviation 5.11
Alanine Aminotransferase (ALT) Week 8	15.1 milligrams per decileter (mg/dL) Standard Deviation 9.2	12.9 milligrams per decileter (mg/dL) Standard Deviation 2.84

SECONDARY outcome

Timeframe: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks

Gamma-glutamyl transferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as mean change from baseline.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=16 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=14 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Gamma-Glutamyl Transferase (GGT) Week 2	12.1 milligrams per decileter (mg/dL) Standard Deviation 3.40	11.8 milligrams per decileter (mg/dL) Standard Deviation 4.58
Gamma-Glutamyl Transferase (GGT) Week 4	12.3 milligrams per decileter (mg/dL) Standard Deviation 4.30	11.8 milligrams per decileter (mg/dL) Standard Deviation 5.82
Gamma-Glutamyl Transferase (GGT) Week 6	12.9 milligrams per decileter (mg/dL) Standard Deviation 4.74	12.3 milligrams per decileter (mg/dL) Standard Deviation 6.92
Gamma-Glutamyl Transferase (GGT) Week 8	12.1 milligrams per decileter (mg/dL) Standard Deviation 4.52	11.8 milligrams per decileter (mg/dL) Standard Deviation 5.00

SECONDARY outcome

Timeframe: 2 weeks, 4 weeks, 6 weeks, and 8 weeks

Glomerular filtration rate is estimated based on blood creatinine concentration per standard nephrology practice. Reported as mean change from baseline.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=16 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=14 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Estimated Glomerular Filtration Rate Week 2	108.7 millileters per minute (mL/min) Standard Deviation 11.3	112.0 millileters per minute (mL/min) Standard Deviation 12.9
Estimated Glomerular Filtration Rate Week 4	110.6 millileters per minute (mL/min) Standard Deviation 11.4	111.8 millileters per minute (mL/min) Standard Deviation 12.1
Estimated Glomerular Filtration Rate Week 6	109.2 millileters per minute (mL/min) Standard Deviation 10.2	111.4 millileters per minute (mL/min) Standard Deviation 11.2
Estimated Glomerular Filtration Rate Week 8	108.4 millileters per minute (mL/min) Standard Deviation 11.9	111.8 millileters per minute (mL/min) Standard Deviation 13.8

SECONDARY outcome

Timeframe: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Blood urea nitrogen (BUN) : creatinine (Cr) is a ratio of serum concentrations of two compounds associated with renal function. Reported as mean change from baseline.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=14 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=16 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Blood Urea Nitrogen to Creatinine Ratio Baseline	15.6 Ratio of BUN (mg/dL) to Cr (mg/dL) Standard Deviation 40.8	14.5 Ratio of BUN (mg/dL) to Cr (mg/dL) Standard Deviation 25.2
Blood Urea Nitrogen to Creatinine Ratio Week 2	16.4 Ratio of BUN (mg/dL) to Cr (mg/dL) Standard Deviation 29.0	15.5 Ratio of BUN (mg/dL) to Cr (mg/dL) Standard Deviation 32.4
Blood Urea Nitrogen to Creatinine Ratio Week 4	15.2 Ratio of BUN (mg/dL) to Cr (mg/dL) Standard Deviation 31.5	15.3 Ratio of BUN (mg/dL) to Cr (mg/dL) Standard Deviation 26.4
Blood Urea Nitrogen to Creatinine Ratio Week 6	14.8 Ratio of BUN (mg/dL) to Cr (mg/dL) Standard Deviation 41.4	14.5 Ratio of BUN (mg/dL) to Cr (mg/dL) Standard Deviation 23.4
Blood Urea Nitrogen to Creatinine Ratio Closeout	14.5 Ratio of BUN (mg/dL) to Cr (mg/dL) Standard Deviation 30.9	14.7 Ratio of BUN (mg/dL) to Cr (mg/dL) Standard Deviation 26.3

SECONDARY outcome

Timeframe: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Enumeration of the various subtypes of blood cells (i.e., red blood cells, white blood cells, and platelets), plus indices including mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), and hematocrit. Reported as: % abnormal (i.e., number of participants with an abnormal value compared to the number of participants in the group) and % new abnormals if abnormal counts were noted. Abnormality is assessed according to standards for age and sex measurements under Quest Diagnostics criteria.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=16 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=14 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Complete Blood Count Abnormals Total White Blood Cell Count (Week 2) : number of abnormals	3 participants	2 participants
Complete Blood Count Abnormals Hemoglobin (Week 8) : number of abnormals	0 participants	3 participants
Complete Blood Count Abnormals Hemoglobin (Week 8) : %new abnormals	0 participants	2 participants
Complete Blood Count Abnormals Total Red Blood Cell Count (Week 4): number of abnormals	1 participants	1 participants
Complete Blood Count Abnormals Total Red Blood Cell Count (Week 4) : number of new abnormals	1 participants	1 participants
Complete Blood Count Abnormals Total Red Blood Cell Count (Week 8) : number of abnormal	0 participants	1 participants
Complete Blood Count Abnormals Total Red Blood Cell Count (Week 8) : number of new abnormals	0 participants	1 participants
Complete Blood Count Abnormals Mean Corpuscular Hemoglobin (Week 8) : number of abnormals	1 participants	0 participants
Complete Blood Count Abnormals Mean Corpuscular Hemoglobin (Week 8) : number of new abnormals	1 participants	0 participants
Complete Blood Count Abnormals Hemoglobin (Week 2) : number of abnormals	0 participants	2 participants
Complete Blood Count Abnormals Hemoglobin (Week 2) : number of new abnormals	0 participants	1 participants
Complete Blood Count Abnormals Hemoglobin (Week 4) : number of abnormals	2 participants	2 participants
Complete Blood Count Abnormals Hemoglobin (Week 4) : number of new abnormals	2 participants	1 participants
Complete Blood Count Abnormals Hemoglobin (Week 6) : number of abnormals	1 participants	2 participants
Complete Blood Count Abnormals Hemoglobin (Week 6) : number of new abnormals	1 participants	1 participants
Complete Blood Count Abnormals Total White Blood Cell Count (Week 2) : number of new abnormals	3 participants	0 participants
Complete Blood Count Abnormals Total White Blood Cell Count (Week 4) : number of abnormals	1 participants	2 participants
Complete Blood Count Abnormals Total White Blood Cell Count (Week 4) : number of new abnormals	1 participants	0 participants
Complete Blood Count Abnormals Total White Blood Cell Count (Week 6) : number of abnormals	2 participants	3 participants
Complete Blood Count Abnormals Total White Blood Cell Count (Week 6) : number of new abnormals	2 participants	1 participants
Complete Blood Count Abnormals Total White Blood Cell Count (Week 8) : number of abnormal	1 participants	1 participants
Complete Blood Count Abnormals Total White Blood Cell Count (Week 8) : %new abnormals	1 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Enumeration of total red blood cell count. Reported as mean change from baseline.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=14 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=16 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Total Red Blood Cell Count Total Red Blood Cell Count (Week 2)	.08 mean change from baseline Standard Deviation .22	.04 mean change from baseline Standard Deviation .15
Total Red Blood Cell Count Total Red Blood Cell Count (Week 4)	-.06 mean change from baseline Standard Deviation .20	.04 mean change from baseline Standard Deviation .20
Total Red Blood Cell Count Total Red Blood Cell Count (Week 6)	-.04 mean change from baseline Standard Deviation .16	.07 mean change from baseline Standard Deviation .23
Total Red Blood Cell Count Total Red Blood Cell Count (Week 8)	.00 mean change from baseline Standard Deviation .23	.08 mean change from baseline Standard Deviation .24

SECONDARY outcome

Timeframe: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Enumeration of total white blood cell count. Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=14 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=16 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Total White Blood Cell Count Total White Blood Cell Count (Week 2)	-.05 thousand cells per microliter (1000/uL) Standard Deviation 1.00	-.59 thousand cells per microliter (1000/uL) Standard Deviation 1.19
Total White Blood Cell Count Total White Blood Cell Count (Week 4)	-.05 thousand cells per microliter (1000/uL) Standard Deviation .98	-.09 thousand cells per microliter (1000/uL) Standard Deviation 1.82
Total White Blood Cell Count Total White Blood Cell Count (Week 6)	.23 thousand cells per microliter (1000/uL) Standard Deviation 1.17	-.24 thousand cells per microliter (1000/uL) Standard Deviation 1.60
Total White Blood Cell Count Total White Blood Cell Count (Week 8)	.21 thousand cells per microliter (1000/uL) Standard Deviation .76	-.24 thousand cells per microliter (1000/uL) Standard Deviation 1.44

SECONDARY outcome

Timeframe: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Enumeration of platelet count. Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=14 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=16 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Platelet Count Platelet Count (Week 2)	3.54 thousand cells per microliter (1000/uL) Standard Deviation 24.05	2.60 thousand cells per microliter (1000/uL) Standard Deviation 26.04
Platelet Count Platelet Count (Week 4)	3.46 thousand cells per microliter (1000/uL) Standard Deviation 19.62	0.07 thousand cells per microliter (1000/uL) Standard Deviation 19.86
Platelet Count Platelet Count (Week 6)	14.00 thousand cells per microliter (1000/uL) Standard Deviation 32.01	22.93 thousand cells per microliter (1000/uL) Standard Deviation 41.90
Platelet Count Platelet Count (Week 8)	10.46 thousand cells per microliter (1000/uL) Standard Deviation 25.62	7.14 thousand cells per microliter (1000/uL) Standard Deviation 20.47

SECONDARY outcome

Timeframe: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Enumeration of mean corpuscular volume (MCV). Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=14 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=16 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Mean Corpuscular Volume Mean Corpuscular Volume (Week 2)	.14 femtoliter (fL) Standard Deviation .76	.20 femtoliter (fL) Standard Deviation 1.21
Mean Corpuscular Volume Mean Corpuscular Volume (Week 4)	.61 femtoliter (fL) Standard Deviation 1.45	-0.27 femtoliter (fL) Standard Deviation 1.54
Mean Corpuscular Volume Mean Corpuscular Volume (Week 6)	.04 femtoliter (fL) Standard Deviation 1.47	-0.25 femtoliter (fL) Standard Deviation 1.56
Mean Corpuscular Volume Mean Corpuscular Volume (Week 8)	.04 femtoliter (fL) Standard Deviation .80	-0.63 femtoliter (fL) Standard Deviation 1.88

SECONDARY outcome

Timeframe: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Enumeration of mean corpuscular hemoglobin (MCH). Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=14 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=16 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Mean Corpuscular Hemoglobin Mean Corpuscular Hemoglobin (Week 2)	0.05 picograms (pg) Standard Deviation 0.35	-0.06 picograms (pg) Standard Deviation 0.45
Mean Corpuscular Hemoglobin Mean Corpuscular Hemoglobin (Week 4)	0.26 picograms (pg) Standard Deviation 0.53	-0.04 picograms (pg) Standard Deviation 0.51
Mean Corpuscular Hemoglobin Mean Corpuscular Hemoglobin (Week 6)	0.29 picograms (pg) Standard Deviation 0.42	-0.13 picograms (pg) Standard Deviation 0.76
Mean Corpuscular Hemoglobin Mean Corpuscular Hemoglobin (Week 8)	0.20 picograms (pg) Standard Deviation 0.52	-0.23 picograms (pg) Standard Deviation 0.87

SECONDARY outcome

Timeframe: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Enumeration of hematocrit. Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.

Outcome measures

Outcome measures
Measure	Placebo Oral Capsule n=14 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=16 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Hematocrit Hematocrit (Week 2)	0.77 percent (%) Standard Deviation 1.92	0.48 percent (%) Standard Deviation 1.49
Hematocrit Hematocrit (Week 4)	-0.20 percent (%) Standard Deviation 1.56	0.23 percent (%) Standard Deviation 2.18
Hematocrit Hematocrit (Week 6)	-0.32 percent (%) Standard Deviation 1.60	0.57 percent (%) Standard Deviation 2.11
Hematocrit Hematocrit (Week 8)	-0.03 percent (%) Standard Deviation 2.16	0.44 percent (%) Standard Deviation 2.27

Adverse Events

Xanthohumol

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo Oral Capsule

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Ryan Bradley, ND, MPH

National University of Natural Medicine

Phone: 5035521862

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo Oral Capsule n=14 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=16 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Change in Plasma Inflammatory Markers Week 6: TNFa	-4 picogram per milliliter (pg/mL) Standard Deviation 10	-23 picogram per milliliter (pg/mL) Standard Deviation 102
Change in Plasma Inflammatory Markers Week 2: Interleukin 1-beta (IL-1b)	220 picogram per milliliter (pg/mL) Standard Deviation 358	-2463 picogram per milliliter (pg/mL) Standard Deviation 12960
Change in Plasma Inflammatory Markers Week 4: IL-1b	172 picogram per milliliter (pg/mL) Standard Deviation 677	-3153 picogram per milliliter (pg/mL) Standard Deviation 12490
Change in Plasma Inflammatory Markers Week 6: IL-1b	2368 picogram per milliliter (pg/mL) Standard Deviation 7689	-620 picogram per milliliter (pg/mL) Standard Deviation 16359
Change in Plasma Inflammatory Markers Week 8: IL-1b	-133 picogram per milliliter (pg/mL) Standard Deviation 328	-3624 picogram per milliliter (pg/mL) Standard Deviation 12306
Change in Plasma Inflammatory Markers Week 2: Interleukin 6 (IL-6)	-54 picogram per milliliter (pg/mL) Standard Deviation 252	-784 picogram per milliliter (pg/mL) Standard Deviation 2795
Change in Plasma Inflammatory Markers Week 4: IL-6	-79 picogram per milliliter (pg/mL) Standard Deviation 263	-684 picogram per milliliter (pg/mL) Standard Deviation 2552
Change in Plasma Inflammatory Markers Week 6: IL-6	-51 picogram per milliliter (pg/mL) Standard Deviation 251	-764 picogram per milliliter (pg/mL) Standard Deviation 2802
Change in Plasma Inflammatory Markers Week 8: IL-6	3565 picogram per milliliter (pg/mL) Standard Deviation 12594	-784 picogram per milliliter (pg/mL) Standard Deviation 2792
Change in Plasma Inflammatory Markers Week 2: Interleukin 8 (IL-8)	1796 picogram per milliliter (pg/mL) Standard Deviation 6380	-5914 picogram per milliliter (pg/mL) Standard Deviation 22847
Change in Plasma Inflammatory Markers Week 4: IL-8	-7 picogram per milliliter (pg/mL) Standard Deviation 352	7669 picogram per milliliter (pg/mL) Standard Deviation 62489
Change in Plasma Inflammatory Markers Week 6: IL-8	276 picogram per milliliter (pg/mL) Standard Deviation 840	-6955 picogram per milliliter (pg/mL) Standard Deviation 25976
Change in Plasma Inflammatory Markers Week 8: IL-8	2639 picogram per milliliter (pg/mL) Standard Deviation 6116	-6882 picogram per milliliter (pg/mL) Standard Deviation 25878
Change in Plasma Inflammatory Markers Week 2: Interleukin 10 (IL-10)	76 picogram per milliliter (pg/mL) Standard Deviation 273	-46 picogram per milliliter (pg/mL) Standard Deviation 180
Change in Plasma Inflammatory Markers Week 4: IL-10	10 picogram per milliliter (pg/mL) Standard Deviation 44	-34 picogram per milliliter (pg/mL) Standard Deviation 150
Change in Plasma Inflammatory Markers Week 6: IL-10	-2 picogram per milliliter (pg/mL) Standard Deviation 17	-49 picogram per milliliter (pg/mL) Standard Deviation 177
Change in Plasma Inflammatory Markers Week 8: IL-10	-3 picogram per milliliter (pg/mL) Standard Deviation 13	-43 picogram per milliliter (pg/mL) Standard Deviation 171
Change in Plasma Inflammatory Markers Week 2: Interleukin 12p70 (IL-12p70)	2 picogram per milliliter (pg/mL) Standard Deviation 9	25 picogram per milliliter (pg/mL) Standard Deviation 154
Change in Plasma Inflammatory Markers Week 4: IL-12p70	3 picogram per milliliter (pg/mL) Standard Deviation 12	-7 picogram per milliliter (pg/mL) Standard Deviation 52
Change in Plasma Inflammatory Markers Week 6: IL-12p70	-2 picogram per milliliter (pg/mL) Standard Deviation 12	-14 picogram per milliliter (pg/mL) Standard Deviation 46
Change in Plasma Inflammatory Markers Week 8: IL-12p70	1 picogram per milliliter (pg/mL) Standard Deviation 9	0 picogram per milliliter (pg/mL) Standard Deviation 55
Change in Plasma Inflammatory Markers Week 2: Tumor Necrosis Factor Alpha (TNFa)	2 picogram per milliliter (pg/mL) Standard Deviation 9	-8 picogram per milliliter (pg/mL) Standard Deviation 124
Change in Plasma Inflammatory Markers Week 4: TNFa	-3 picogram per milliliter (pg/mL) Standard Deviation 9	-28 picogram per milliliter (pg/mL) Standard Deviation 100
Change in Plasma Inflammatory Markers Week 8: TNFa	-1 picogram per milliliter (pg/mL) Standard Deviation 8	-25 picogram per milliliter (pg/mL) Standard Deviation 100

Measure	Placebo Oral Capsule n=16 Participants Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.	Xanthohumol n=14 Participants Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary 6-Prenylnaringenin (6-PN): Baseline	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary 6-PN: Week 2	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary 6-PN: Week 4	.591 nanograms per millileter (ng/mL) Standard Deviation 2.132	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary 6-PN: Week 6	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary 6-PN: Week 8	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary 8-Prenylnaringenin (8-PN): Baseline	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary 8-PN: Week 2	6.811 nanograms per millileter (ng/mL) Standard Deviation 12.029	1.412 nanograms per millileter (ng/mL) Standard Deviation 3.877
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary 8-PN: Week 4	6.588 nanograms per millileter (ng/mL) Standard Deviation 0.840	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary 8-PN: Week 6	7.196 nanograms per millileter (ng/mL) Standard Deviation 14.662	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary 8- PN Week 8	4.725 nanograms per millileter (ng/mL) Standard Deviation 7.769	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary Dihydroxanthohumol (DXN): Baseline	0 nanograms per millileter (ng/mL) Standard Deviation 0	.086 nanograms per millileter (ng/mL) Standard Deviation .312
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary DXN: Week 2	.562 nanograms per millileter (ng/mL) Standard Deviation .542	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary DXN: Week 4	.561 nanograms per millileter (ng/mL) Standard Deviation .522	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary DXN: Week 6	.410 nanograms per millileter (ng/mL) Standard Deviation .325	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary DXN: Week 8	2.043 nanograms per millileter (ng/mL) Standard Deviation 4.702	.016 nanograms per millileter (ng/mL) Standard Deviation .059
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary Desmethyldihydroxanthohumol (DDXN): Baseline	.042 nanograms per millileter (ng/mL) Standard Deviation .152	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary DDXN: Week 2	.041 nanograms per millileter (ng/mL) Standard Deviation .148	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary DDXN: Week 4	.036 nanograms per millileter (ng/mL) Standard Deviation .131	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary DDXN: Week 6	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary DDXN: Week 8	.071 nanograms per millileter (ng/mL) Standard Deviation .257	.023 nanograms per millileter (ng/mL) Standard Deviation .083
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary Isoxanthohumol (IXN): Baseline	2.237 nanograms per millileter (ng/mL) Standard Deviation 4.364	.299 nanograms per millileter (ng/mL) Standard Deviation 1.080
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary IXN: Week 2	94.120 nanograms per millileter (ng/mL) Standard Deviation 82.500	2.121 nanograms per millileter (ng/mL) Standard Deviation 4.001
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary IXN: Week 4	103.920 nanograms per millileter (ng/mL) Standard Deviation 75.201	.494 nanograms per millileter (ng/mL) Standard Deviation 1.782
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary IXN: Week 6	66.628 nanograms per millileter (ng/mL) Standard Deviation 41.899	.281 nanograms per millileter (ng/mL) Standard Deviation 1.012
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary IXN: Week 8	95.756 nanograms per millileter (ng/mL) Standard Deviation 83.275	.484 nanograms per millileter (ng/mL) Standard Deviation 1.745
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary Xanthohumol (XN) Baseline	1.952 nanograms per millileter (ng/mL) Standard Deviation 13.967	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary XN: Week 2	21.280 nanograms per millileter (ng/mL) Standard Deviation 12.112	4.666 nanograms per millileter (ng/mL) Standard Deviation 16.440
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary XN: Week 4	14.908 nanograms per millileter (ng/mL) Standard Deviation 8.667	.124 nanograms per millileter (ng/mL) Standard Deviation .448
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary XN: Week 6	19.979 nanograms per millileter (ng/mL) Standard Deviation 12.242	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Urinary XN: Week 8	19.952 nanograms per millileter (ng/mL) Standard Deviation 13.967	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma 6-Prenylnaringenin (6PN): Baseline	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma 6-PN: Week 2	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma 6-PN: Week 4	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma 6-PN: Week 6	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma 6-PN: Week 8	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma 8-Prenylnaringenin: Baseline	1.302 nanograms per millileter (ng/mL) Standard Deviation 3.034	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma 8-PN: Week 2	1.503 nanograms per millileter (ng/mL) Standard Deviation 3.340	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma 8-PN: Week 4	.840 nanograms per millileter (ng/mL) Standard Deviation 3.144	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma 8-PN: Week 6	1.001 nanograms per millileter (ng/mL) Standard Deviation 2.563	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma 8-PN: Week 8	1.302 nanograms per millileter (ng/mL) Standard Deviation 3.034	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma Dihydroxanthohumol (DXN): Baseline	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma DXN: Week 2	.968 nanograms per millileter (ng/mL) Standard Deviation 3.622	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma DXN: Week 4	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma DXN: Week 6	0 nanograms per millileter (ng/mL) Standard Deviation 0	7.288 nanograms per millileter (ng/mL) Standard Deviation 25.245
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma DXN: Week 8	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma Desmethyldihydroxanthohumol (DDXN): Baseline	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma DDXN: Week 2	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma DDXN: Week 4	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma DDXN: Week 6	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma DDXN: Week 8	0 nanograms per millileter (ng/mL) Standard Deviation 0	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma Isoxanthohumol (IXN): Baseline	0 nanograms per millileter (ng/mL) Standard Deviation 0	.275 nanograms per millileter (ng/mL) Standard Deviation .992
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma IXN: Week 2	7.864 nanograms per millileter (ng/mL) Standard Deviation 4.135	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma IXN: Week 4	6.999 nanograms per millileter (ng/mL) Standard Deviation 3.514	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma IXN: Week 6	6.140 nanograms per millileter (ng/mL) Standard Deviation 3.565	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma IXN: Week 8	8.174 nanograms per millileter (ng/mL) Standard Deviation 3.794	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma Xanthohumol (XN): Baseline	0 nanograms per millileter (ng/mL) Standard Deviation 0	.365 nanograms per millileter (ng/mL) Standard Deviation .974
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma XN: Week 2	7.156 nanograms per millileter (ng/mL) Standard Deviation 3.888	1.325 nanograms per millileter (ng/mL) Standard Deviation 3.424
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma XN: Week 4	6.784 nanograms per millileter (ng/mL) Standard Deviation 3.497	0 nanograms per millileter (ng/mL) Standard Deviation 0
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma XN: Week 6	5.810 nanograms per millileter (ng/mL) Standard Deviation 3.153	.822 nanograms per millileter (ng/mL) Standard Deviation 2.304
Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine Plasma XN: Week 8	5.796 nanograms per millileter (ng/mL) Standard Deviation 3.188	0 nanograms per millileter (ng/mL) Standard Deviation 0

Other adverse events
Measure	Xanthohumol n=16 participants at risk Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. Xanthohumol: The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.	Placebo Oral Capsule n=14 participants at risk Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal. Placebo oral capsule: The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.
Ear and labyrinth disorders Tinnitus	0.00% 0/16 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Respiratory, thoracic and mediastinal disorders Nasal congestion	18.8% 3/16 • Number of events 5 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	28.6% 4/14 • Number of events 4 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
General disorders Allergy symptoms	18.8% 3/16 • Number of events 4 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	21.4% 3/14 • Number of events 6 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Gastrointestinal disorders Abdominal pain	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	14.3% 2/14 • Number of events 3 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Gastrointestinal disorders Decreased appetite	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Eye disorders Dry eyes and periorbital twitching	0.00% 0/16 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	14.3% 2/14 • Number of events 3 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Gastrointestinal disorders Constipation	18.8% 3/16 • Number of events 4 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	28.6% 4/14 • Number of events 4 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Gastrointestinal disorders Diarrhea	12.5% 2/16 • Number of events 2 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	21.4% 3/14 • Number of events 4 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Gastrointestinal disorders Indigestion	12.5% 2/16 • Number of events 3 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	21.4% 3/14 • Number of events 4 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
General disorders Increased thirst	0.00% 0/16 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	14.3% 2/14 • Number of events 3 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
General disorders Headache	25.0% 4/16 • Number of events 4 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	21.4% 3/14 • Number of events 3 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Psychiatric disorders Restlessness	0.00% 0/16 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Psychiatric disorders Agitation	0.00% 0/16 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Psychiatric disorders Anxiety	0.00% 0/16 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	14.3% 2/14 • Number of events 3 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Psychiatric disorders Depression	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Psychiatric disorders Irritability	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	14.3% 2/14 • Number of events 2 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
General disorders Lethargy	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
General disorders Insomnia	0.00% 0/16 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	28.6% 4/14 • Number of events 6 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
General disorders Fatigue	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
General disorders Hyperactivity	0.00% 0/16 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Respiratory, thoracic and mediastinal disorders Shortness of breath on exertion	12.5% 2/16 • Number of events 2 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Cardiac disorders Hypotension	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	0.00% 0/14 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Respiratory, thoracic and mediastinal disorders Chest pain	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	0.00% 0/14 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Vascular disorders Peripheral edema/swelling	0.00% 0/16 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Skin and subcutaneous tissue disorders Acne	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 2 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Skin and subcutaneous tissue disorders Itchy/dry skin	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Reproductive system and breast disorders Breast swelling	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 2 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
General disorders Dizziness	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	0.00% 0/14 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
General disorders Sore throat	6.2% 1/16 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	21.4% 3/14 • Number of events 4 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
Renal and urinary disorders Decreased urination	0.00% 0/16 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
General disorders Fever	0.00% 0/16 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death
General disorders General body pain	0.00% 0/16 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death	7.1% 1/14 • Number of events 1 • 8 weeks Mild/Grade 1: No intervention; asymptomatic lab or radiographic findings; marginal clinical significance Moderate/Grade 2: OTC or single-physician visit; AE limited activities of daily living for \<48hrs Severe/Grade 3: AE significantly limited basic self-care but did not require initial hospitalization or prolongation of hospitalization; Not immediately life-threatening but disabling Serious/Grade 4: Life threatening Serious/Grade 5: Death